Verb Biotics’ Keystone Postbiotic enriches 33 beneficial gut species, trial finds

A clinical trial and mechanistic study on Verb Biotics’ Keystone ingredient find that the oat-based postbiotic enriched 33 beneficial “keystone” gut bacteria, reduced 38 taxa linked to gastrointestinal distress, and showed associated improvements in stress, emotional well-being, and inflammatory biomarkers. 

Keystone Postbiotic was designed to address a need for a low-dose, stable, and easy-to-formulate biotic that supports gut health, emotional wellness, and whole-body resilience. 

Verb Biotics notes that the ingredient works alongside microbes in the gut to release metabolites that act as “gut fertilizers” to deliver a prebiotic and postbiotic effect that strengthens the ecosystem from within.

Nutrition Insight speaks with the Verb Biotics team to explore the findings of these studies, the importance of selective microbiome modulation, and next steps.

“These studies show that a postbiotic can do more than provide general gut-health support; it can selectively strengthen beneficial microbes already present in the gut,” Todd Beckman, CEO of Verb Biotics, tells us. “I hope they raise the standard for the category by encouraging brands to look for ingredients with both a defined mechanism and human clinical validation.”

Beckman hopes the studies raise the evidence standard across the postbiotic category.“Keystone also gives brands a practical way to bring microbiome benefits into foods, beverages, and supplements that are difficult to formulate with live probiotics or gram-level prebiotics. Ultimately, the impact should be more effective microbiome products in formats consumers can use every day.”

Boosting beneficial species

Keystone is created using two lactic acid bacterial strains, Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum 276, which ferment oat flour, followed by pasteurization and freeze-drying to produce the postbiotic. Verb Biotics notes it releases bioactive metabolites at a daily dose of 300 mg.

The study, published in Beneficial Microbes, tested the ingredient in a four-week, randomized, double-blind trial in 76 generally healthy adults, who consumed capsules containing either a placebo or Keystone at 300 mg per day.

The researchers analyzed stool samples collected at baseline and week four with shotgun metagenomic sequencing and mapped key signaling proteins, metabolites, and hormones. Participants also filled out questionnaires on psychological distress and health-related quality of life.

The study finds that Keystone boosted 33 beneficial species, including up to 243-fold enrichment of Akkermansia and 9.6-fold enrichment of Bifidobacterium. It reduced 38 species linked to gastrointestinal distress, such as Haemophilus and Prevotella.

Moreover, the researchers found an improvement in a key inflammatory signaling protein that they note reflects a more balanced immune profile. 

An accompanying mechanistic study details how Keystone achieves the observed effects. This study evaluated Keystone’s potential to deliver health benefits by modulating the host immune system and gut microbiome. 

Delebecque explains that Keystone boosts bifidobacteria to feed lactate and acetate to butyrate producers.The preclinical models used in this study indicate that Keystone protects intestinal barrier integrity and drives a 6.48-fold increase in native Bifidobacterium, accelerated wound healing, and supported resistance to oxidative stress.

Camille Delebecque, Ph.D., head of Biotechnology at Verb Biotics, says that the two papers paint a coherent picture as both showed increases in Bifidobacterium, while the clinical trial found the postbiotic enriched other species as well.

“This is the cross-feeding cascade the mechanism predicts, in which bifidobacteria feed lactate and acetate to butyrate producers. Serum butyrate trended upward over the same period.”

He says that the cell and nematode models — a study on Caenorhabditis elegans roundworms — add another dimension, as these showed barrier protection and resilience to oxidative stress, highlighting a plausible route for the improved emotional well-being that participants reported.

Selective microbiome modulation

Noah Zimmerman, Ph.D., Verb Biotics’ CSO, highlights the significance of Keystone’s selective microbiome modulation, rather than a broad prebiotic effect.

“Not all bacteria can use the same prebiotics as carbon sources. That specificity is the basis of the whole effect and was a requirement with a dose of only 300 mg, whereas conventional prebiotics work at the gram scale as a bulk fermentable substrate. With Keystone, metabolites and molecules from both the oats as well as the bacteria feed specific bacteria in the gut.”

“For instance, the beta-glucans from the oats are unprocessed by the lactic acid bacteria during fermentation, so they reach the colon intact.”

Zimmerman explains that Keystone’s entry point was engineered around the bifidogenic effect. “Bifidobacteria don’t produce butyrate themselves but release lactate and acetate that butyrate producers feed on.”

Zimmerman says Keystone’s specificity is the basis of the whole effect and was a requirement with a dose of 300 mg.He says that designing Keystone for specific cross-feeding mechanisms is what makes the downstream pattern specific rather than general. “Therefore, specific functional groups move within a stable community, as evidenced in the clinical trial, rather than the whole community moving. This also reduces the risk of side effects — no adverse events were observed.”

Species-level changes

Delebecque explains that the trial was not designed to determine a correlation between the abundance of a specific species, such as Akkermansia, and clinical outcomes.

“The wider clinical literature does link Akkermansia to mucosal barrier integrity and metabolic health, though most of that work involves supplemented Akkermansia rather than endogenous enrichment,” he explains.

“What makes this endogenous enrichment strategy interesting is based on the fact that Akkermansia is hard to deliver directly. It is oxygen, heat, and moisture sensitive, difficult to stabilize and hold viable on the shelf,” Delebecque underscores.

Although the study found species-level changes, the intervention did not affect overall microbiome diversity, which is commonly emphasized in the marketing of probiotics and prebiotics. Zimmerman explains that brands using Verb Biotics’ postbiotic can frame the solution as producing a targeted change in which species dominate.

“Microbial diversity is defined by species richness (number of different bacteria present) and evenness (balance of the population size). With Keystone, the results of the clinical trial demonstrated that the composition of the microbial population shifted toward more beneficial species being present in greater abundance and potential opportunistic pathogens being decreased.”

Building health solutions

In addition to microbial changes in the gut, 68% of participants using Keystone reported improved emotional well-being. Moreover, the researchers found a healthier relationship between starting and follow-up morning cortisol in this group, with the greatest correction in people with an elevated baseline cortisol.

“We saw encouraging positive effects of Keystone Postbiotic on cortisol, inflammatory markers, and reported emotional well-being for participants during the trial,” says Zimmerman.

The clinical trial also found improvements in emotional well-being, though this needs to be validated in future studies.“To support further health claims, we would like to expand this work into a larger population to see how robust the effects on these biomarkers are. What matters most is how people feel when they are using the postbiotic. Can they feel the effect?”

To assess this in future studies, he says the team would like to pair biomarker data with qualified questionnaires for emotional well-being, but in a population that has room to improve. “In this trial, most participants scored in the normal range at both visits, which limits what we can detect.”

Next-gen biotics pipeline

Beckman says that Keystone is one part of a broader next-generation biotics pipeline Verb Biotics is building around specific, measurable health outcomes. For example, earlier this year, a clinical trial found that its Lp815 probiotic improved sleep quality, reduced stress, and increased urinary gamma-aminobutyric acid (GABA) levels. 

“A major focus is metabolic health, including healthy lipid and glucose regulation and the growing question of what comes next after GLP-1 therapy. Many consumers will need support maintaining their weight, body composition, and broader metabolic health after treatment, and we believe the microbiome can be part of that solution.”

He adds that the company is also developing targeted approaches for foundational microbiome health, digestive function, immune balance, and allergy support. “These programs are intended to provide daily, long-term health support rather than acute treatment.”

“Across the pipeline, our goal is to create clinically validated ingredients that can move beyond capsules into functional foods, beverages, and other everyday formats,” Beckman concludes.